The loss of teeth due to the progressive destruction of the tooth attachment is one of the major health problems in America. Cementum is a unique tissue specifically adapted to provide support for anchoring collagenous fibers to mineralized matrix in an environment where repetitive forces are applied. Currently, the mechanisms involved in the recruitment and differentiation of cementoblasts, cells responsible for forming unique cementum matrix, are largely unknown. Using our combined in vitro/in vivo model of human cementogenesis we have established that human cementum-derived cells exhibit a putative "cementum morphogenetic" activity (PCMA). This PCMA results in an apparent "phenotypic switch" of bone marrow stromal cells (BMSC) into cementoblasts. Under normal conditions, BMSC do not exhibit any major features of cementoblastic phenotype. In this application, as a first step towards general goal of delineating mechanisms involved in cementoblastic differentiation, we propose to establish the nature of the PCMA exhibited by human cementum-derived cells (i.e., whether it is dependent on secreted molecules or associated with the cellular fraction) and to develop a more defined system that will provide the experimental basis for subsequent studies aiming at identifying factor(s) responsible for PCMA. [unreadable] [unreadable] Aim 1. to establish whether the putative "cementum morphogenetic" activity is associated only with cellular fraction or with medium fraction of human cementum-derived cells (HCDC) as well; [unreadable] Aim 2. to test the hypothesis that the putative "cementum morphogenetic" activity can be achieved without viable cementogenic cells present in the in vitro/in vivo experimental system; [unreadable] [unreadable] The ultimate goal of this research is identify factors that play key roles in the induction of cementoblastic phenotype in noncommitted cells. If such morphogenetic factor(s) can be isolated and identified, it will be of clear potential for clinical use. [unreadable] [unreadable]